517 research outputs found

    “In dem Ozean vergessener Opfer die Spur einer jungen Frau zu finden". Memorie transculturali in "Sie kam aus Mariupol" di Natascha Wodin

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    In "Veniva da Mariupol" (Sie kam aus Mariupol, 2017) l’autrice/narratrice, nata in Germania da genitori di origine ucraina, si mette sulle tracce della madre, deportata in Germania come Zwangsarbeiterin. Ne emerge un impressionante e oscuro panorama del XX secolo. La giovane donna assiste alla caduta della sua famiglia aristocratica – nella quale ci sono anche antenati italiani – nel terrore stalinista, e nel 1944 arriva con il marito per il lavoro coatto in Germania, dove dopo la fine della guerra sarà una “displaced person”. Nella sua ricerca Wodin mostra come il passato e la storia, in una dimensione individuale che si fa collettiva, possano essere recuperati attraverso la narrazione da chi non è stato testimone e quali spazi di memoria transnazionali si configurino in questi drammatici movimenti da est a ovest. In questo modo si pone anche l’importante questione della natura delle dinamiche nazionali e transnazionali che possono impedire la competizione delle vittime attraverso memorie collegate: né per relativizzare la memoria della Shoah, né per banalizzare le ferite storiche di altri gruppi di vittime trascurati o rimossi dalla storia ufficiale

    Tra Est e Ovest. Poetiche del movimento nell’opera di Natascha Wodin

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    Movement and mobility characterize the biographies and texts of many contemporary authors who were forced to leave their own homelands not only as a result of conflict, war, and repression, but also because of their free existential choices, thus triggering new dynamics that continuously enrich the literary landscape. The work of the writers who paved the way for transcultural relations between East and West Europe is particularly interesting from the transareal perspective (Ottmar Ette) which refers to interconnected areas at an international, national, regional, and local level. This is the context in which the novels of Natascha Wodin – award-winning author for "Sie kam aus Mariupol" (2017, She Came from Mariupol) –, are set. This article will analyse two novels by the author: "Nachtgeschwister" (2009), her tormented autobiographical story, which is also about her comings and goings in the city of Berlin, and "Irgendwo in diesem Dunkel" (2018), the dramatic story of a denied belonging to places and homes. The protagonists and narrators of the two works mentioned above move through and endeavour to take refuge in urban settings, represented by eastern and western places, often described as dark, hidden, and interstitial places. These wandering lives reveal how European history was marked by persecution, violence and dislocations, as well as the painful and hard-fought search for a new and vital freedom of movement, which is also characterized by personal challenge and the ethics of cohabitation

    Mitochondrial targeting of cyclosporin A enables selective inhibition of cyclophilin-D and enhanced cytoprotection after glucose and oxygen deprivation

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    CsA (cyclosporin A) is a hydrophobic undecapeptide that inhibits CyPs (cyclophilins), a family of PPIases (peptidylprolyl cis–trans isomerases). In some experimental models, CsA offers partial protection against lethal cell injury brought about by transient ischaemia; this is believed to reflect inhibition of CyP-D, a mitochondrial isoform that facilitates formation of the permeability transition pore in the mitochondrial inner membrane. To evaluate this further, we have targeted CsA to mitochondria so that it becomes selective for CyP-D in cells. This was achieved by conjugating the inhibitor to the lipophilic triphenylphosphonium cation, enabling its accumulation in mitochondria due to the inner membrane potential. In a cell-free system and in B50 neuroblastoma cells the novel reagent (but not CsA itself) preferentially inhibited CyP-D over extramitochondrial CyP-A. In hippocampal neurons, mitochondrial targeting markedly enhanced the capacity of CsA to prevent cell necrosis brought about by oxygen and glucose deprivation, but largely abolished its capacity to inhibit glutamate-induced cell death. It is concluded that CyP-D has a major pathogenic role in ‘energy failure’, but not in glutamate excitotoxicity, where cytoprotection primarily reflects CsA interaction with extramitochondrial CyPs and calcineurin. Moreover, the therapeutic potential of CsA against ischaemia/reperfusion injuries not involving glutamate may be improved by mitochondrial targeting

    Chronic cocaine administration modulates the expression of transcription factors involved in midbrain dopaminergic neuron function

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    Chronic cocaine use leads to pronounced alterations in neuronal functions in brain circuits associated with reward. In the present study, we examined in the rat midbrain the effects of acute, subchronic (5 days) and chronic cocaine treatments (14 days) on the gene expression of transcription factors involved in the development and maintenance of dopaminergic neurons. We show that chronic, but not acute or subchronic, cocaine administration downregulates Nurr1 and Pitx3 transcripts whereas En1 transcripts are upregulated. Conversely, Lmx1b and En2 transcripts are not affected by the drug treatment, indicating that the modulation of the midbrain transcription factors analyzed is highly selective. Interestingly, modification of the gene expression for these transcription factors persists in midbrain as long as two weeks after the last drug administration, suggesting that it may account for some of the enduring alterations in midbrain dopaminergic circuits associated with chronic cocaine us

    Balance between excitation and inhibition controls the temporal organization of neuronal avalanches

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    Neuronal avalanches, measured in vitro and in vivo, exhibit a robust critical behavior. Their temporal organization hides the presence of correlations. Here we present experimental measurements of the waiting time distribution between successive avalanches in the rat cortex in vitro. This exhibits a nonmonotonic behavior not usually found in other natural processes. Numerical simulations provide evidence that this behavior is a consequence of the alternation between states of high and low activity, named up and down states, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods, both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homeostatic mechanisms

    Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro

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    The transcription factor Nurr1 is essential for the generation of midbrain dopaminergic neurons (mDA). Only a few Nurr1-regulated genes have so far been identified and it remains unclear how Nurr1 influences the development and function of dopaminergic neurons. To identify novel Nurr1 target genes we have used genome-wide expression profiling in rat midbrain primary cultures, enriched in dopaminergic neurons, following up-regulation of Nurr1 expression by depolarization. In this study we demonstrate that following depolarization the hyperexpression of Nurr1 and the brain derived neurotrophic factor (BDNF) are phospholipase C- and protein kinase C-dependent. We show that Bdnf, which encodes a neurotrophin involved also in the phenotypic maturation of mDA neurons, is a novel Nurr1 target gene. By RNA interference experiments we show that a decreased Nurr1 expression is followed by tyrosine hydroxylase and BDNF mRNA and protein down-regulation. Reporter gene assay experiments performed on midbrain primary cultures using four Bdnf promoter constructs show that Bdnf is a direct target gene of Nurr1. Taken together, our findings suggest that Nurr1 might also influence the development and the function of midbrain dopaminergic neurons via direct regulation of Bdnf expression. © 2007 The Authors

    Methylphenidate administration determines enduring changes in neuroglial network in rats

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    Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring

    Quantifying barcodes of dendritic spines using entropy-based metrics

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    Spine motility analysis has become the mainstay for investigating synaptic plasticity but is limited in its versatility requiring complex, non automatized instrumentations. We describe an entropy-based method for determining the spatial distribution of dendritic spines that allows successful estimation of spine motility from still images. This method has the potential to extend the applicability of spine motility analysis to ex vivo preparations

    Enhancement of Dopaminergic Differentiation in Proliferating Midbrain Neuroblasts by Sonic Hedgehog and Ascorbic Acid

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    We analyzed the molecular mechanisms involved in the acquisition and maturation of dopaminergic (DA) neurons generated in vitro from rat ventral mesencephalon (MES) cells in the presence of mitogens or specific signaling molecules. The addition of basic fibroblast growth factor (bFGF) to MES cells in serum-free medium stimulates the proliferation of neuroblasts but delays DA differentiation. Recombinant Sonic hedgehog (SHH) protein increases up to three fold the number of tyrosine hydroxylase (TH)-positive cells and their differentiation, an effect abolished by anti-SHH antibodies. The expanded cultures are rich in nestin-positive neurons, glial cells are rare, all TH+ neurons are DA, and all DA and GABAergic markers analyzed are expressed. Adding ascorbic acid to bFGF/SHH-treated cultures resulted in a further five- to seven-fold enhancement of viable DA neurons. This experimental system also provides a powerful tool to generate DA neurons from single embryos. Our strategy provides an enriched source of MES DA neurons that are useful for analyzing molecular mechanisms controlling their function and for experimental regenerative approaches in DA dysfunction
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